Aicardi’sDiseases of the Nervous System in Childhood4th EditionEdited by Alexis Arzimanoglou with Anne O’Hare, Michael Johnston and Robert Ouvrier

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Aicardi’s Diseases of the Nervous System in Childhood 4th EditionEdited by Alexis Arzimanoglou with Anne O’Hare, Michael Johnston and Robert Ouvrier

The Premier Textbook of Clinical Child NeurologyThis classic text on paediatric neurology is now in its fourth edition. Leading academics from around the world present evidence from their various areas of expertise, placing it firmly in the clinical context. Each chapter covers the basic science of the disorder and relevant genetic advances. New to this edition are chapters on fetal neurology, movement disorders, basal ganglia disease and psychogenic disorders. Ref-erences at the end of each chapter are thorough, guiding the clinician to relevant further reading. The inter-national team of editors has maintained the clinical approach of the late Jean Aicardi, which distinguishes this book from others in the field. Succinctly given, patient-focused information makes Aicardi’s Diseases of Nervous System in Childhood a comprehensive yet readable resource for busy clinicians in paediatric neurology, general paediatrics, neurodisability and all the related medical disciplines.

• Covers large areas of paediatric neurology• Patient-focussed with succinct clinical information• Pertinent chapter references for further reading

New for the 4th Edition

NEW Completely revised and updatedNEW International team of expert editors NEW Updates on genetic advancesNEW Sections on Fetal Neurology, Basal Ganglia

and Movement DisordersNEW Easy to use presentationNEW Full colour illustrations throughout

Clinics in Developmental Medicine Series

June 2017 / Hardback / 928 pp / 280 x 205mm, 4-colour / ISBN 978-1-909962-80-4 / £199.95

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Professor Alexis Arzimano-glou is the Director of the Department of Paediatric Clinical Epileptology, Sleep Disorders and Functional Neurology at the Universi-ty Hospitals of Lyon, France and Visiting Professor at the Universitat de Barcelona,

Spain, coordinating the Epilepsy Research Program at the Hospital San Juan de Dios. He graduated from the Salonica University, Greece, trained in Neurology at Great Ormond Street, London, UK and at the Hôpital de la Salpetriere and in Child Neurology as a fellow of Jean Aicardi at the Hôpital des Enfants Malades in Paris, France. He then with worked with Jean Aicardi for over 25 years. He served as: Chair of the Scientific Committee of the European Paediatric Neu-rology Society; Editor-in-Chief of the International League Against Epilepsy (IALE) educational journal Epileptic Disor-ders; Elected member of the European Commission of the ILAE. Together with Jean Aicardi and Renzo Guerrini he authored Aicardi’s Epilepsy in Children. He is the editor of seven books and an author or co-author of over one hundred scientific articles in the fields of cognition, medical and sur-gical treatment of childhood epilepsies.

Professor Anne O’Hare is Professor of Community Pae-diatrics and Director of the Salvesen Mindroom Centre for Learning Difficulties, at the University of Edinburgh. She is a developmental paedi-atrician with extensive clinical experience in neurodisability, neuroscience and child pro-tection. Her research interests include how neurodevelop-mental conditions impact

on the development of speech, language, communication, motor skills and learning and the development of effective interventions.

Professor Michael V John-ston is a Professor of Neurol-ogy, Pediatrics and Physical Medicine and Rehabilitation at the Johns Hopkins Universi-ty School of Medicine and the Chief Medical Officer and the Blum Moser Endowed Profes-sor of Pediatric Neurology at the Kennedy Krieger Institute in Baltimore, Maryland, USA.

He trained in pediatrics, neurology and neuroscience at Johns Hopkins, and his clinical and research interests include fetal and neonatal neurology, as well as care for older children with cerebral palsy and neurogenetic disorders including Rett syn-drome. He has been active in development of strategies to pro-tect the developing brain from hypoxic-ischemic injury. He is one of the founding faculty members of the Neurosciences In-tensive Care Nursery (NICN) research and clinical care group at Johns Hopkins Hospital, and he has also been a leader in of the Phelps Cerebral Palsy Center at Kennedy Krieger.

Professor Robert Ouvrier is the Emeritus Professor of child neurology in the University of Sydney. After training in general paediatrics in Sydney, Perth and Papua-New Guin-ea, he undertook specialist training in child neurology at the Royal Children’s Hospital, Melbourne, the University of Kentucky (1969-70) and the

Johns Hopkins Hospital, Baltimore USA (1971-72). He was then Head of the Department of Neurology at the Children’s Hospital at Westmead, Sydney for 25 years. In 1999, he be-came the Foundation Head of the Institute for Neuroscience and Muscle Research at The Children’s Hospital, Westmead. He was President of the International Child Neurology As-sociation from 2006-2010. He is the author of two books, thirty book chapters and an author or co-author of over 150 scientific articles on paediatric neurology.

Meet the Editors behind this updated and revised new edition

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PART 1: FETAL AND NEONATAL NEUROLOGY1. Fetal Neurology

André Du Plessis and Michael Johnston2. Neurological Diseases in the Perinatal Period

Linda de Vries and Miriam Mbiarge

PART 2: MALFORMATIONS OF CORTICAL DEVELOPMENT, NEUROCUTANEOUS SYNDROMES, GENETIC ANOMALIES and DYSMORPHIC SYNDROMES

3. Malformations of Cortical Development Nadia Bahi-Buisson and Nathalie Boddaert

4. Neurocutaneous Diseases and Syndromes Alexis Arzimanoglou and Eleni Panagiotakaki

5. Genetic Anomalies and Dysmorphic Syndromes Karine Pelc and Bernard Dan

PART 3: NEUROLOGICAL CONSEQUENCES OF PRENATAL, PERINATAL AND EARLY POSTNATAL INTERFERENCE WITH BRAIN DEVELOPMENT

6. Osseous Malformations of the Skull and Craniovertebral Junction Richard Hayward and Dominic Thompson

7. Hydrocephalus and Non-traumatic Pericerebral Collections Andrew Whitelaw and Christian Sainte-Rose

8. Cerebral Palsy and Related Movement Disorders Ingeborg Krageloh-Mann

PART 4: METABOLIC, AND HEREDODEGENERATIVE DISORDERS9. Metabolic Diseases

Linda De Meirleir 10. Heredodgenerative Disorders: Leukodystrophies; Disorders Involving Predominantly the Grey Matter,

Poliodystrophies and Ceroid-Lipofuscinoses; Diffuse CNS Involvement Neuroaxonal Dystrophy; Alexis Arzimanoglou, Victoria San AntonioSpinocerebellar Degenerations

Robert Ouvrier

PART 5: POSTNATAL EXTRINSIC INSULTS 11. Infectious Diseases

Cheryl Hemingway, Michael Eyre and Alasdair Bamford 12. Parainfectious and other Inflammatory Disorders of Immunological Origin

Michael Johnston and Marc Tardieu 13. Accidental and Non-accidental Injuries by Physical and Toxic Agents

Karen Barlow, Robert Forsyth and Robert Minns

PART 6: TUMOURS AND VASCULAR DISORDERS 14. Tumours of the Central Nervous System and other Space-Occupying Lesions

Colin Kennedy, David Walker and Aabir Chakraborty

Table of Contents

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15. Cerebrovascular Disorders Gabrielle de Veber and Adam Kirton

PART 7: PAROXYSMAL DISORDERS 16. Epilepsies and other Seizure Disorders

Alexis Arzimanoglou and Mike Duchowny 17. Headache disorders

Kenneth Mack 18. Sleep Disorders

Patricia Franco

PART 8: MOVEMENT DISORDERS 19. Movement and Basal Ganglia Disorders

Paddy Grattan-Smith, Russell Dale and Emilio Fernandez-Alvarez 20. Tics and Gilles de la Tourette Syndrome

Robert Ouvrier and Russell Dale 21. Non-epileptic Paroxysmal Movement Disorders

Paddy Grattan-Smith

PART 9: DISORDERS OF THE OCULOMOTOR, VISUAL, AUDITORY AND VESTIBULAR SYSTEMS 22. Disorders of Oculomotor, Motor and Visual Functions

Carey Matsuba 23. Disorders of Auditory and Vestibular Functions

Anne O’Hare

PART 10: NEUROMUSCULAR DISEASES 24. Diseases of the Motor Neuron

Francesco Muntoni and Mariacristina Scoto 25. Disorders of the Peripheral Nerves

Robert Ouvrier and Manoj Menezes 26. Muscle Disorders

Monique Ryan, Kathryn North and Francesco Muntoni

PART 11: NEUROLOGICAL MANIFESTATIONS OF SYSTEMIC DISEASES 27. Electrolyte and Acid-Base Metabolism Disturbances, Nutritional Disorders and other Systemic Diseases

Peter Baxter

PART 12: DEVELOPMENTAL AND NEUROPSYCHIATRIC DISORDERS OF CHILDHOOD 28. Neurodevelopmental Disabilities and their Management

Bruce Shapiro 29. Autism Spectrum Disorder and Autistic-like Conditions

Anne O’Hare and Roberto Tuchman 30. Attention-Deficit–Hyperactivity Disorder and Co-existing Impairments

Bruce Shapiro 31. Disorders of Speech, Language and Communication

Anne O’Hare 32. Psychogenic Neurological Disorders

Paddy Grattan-Smith

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Alexis Arzimanoglou Director of the Department of Paediatric Clinical Epileptology, Sleep Disorders and Functional Neurology at the University Hospitals of Lyon, France; Visiting Professor at the Universitat de Barcelona, Spain

Nadia Bahi-Buisson Consultant, Neurologie Unité, Necker-Enfants Malades, Paris, France

Alasdair Bamford Paediatric Infectious Diseases Consultant, Great Ormond Street Hospital, London, UK

Karen Barlow Cumming School of Medicine, University of Calgary

Peter Baxter Sheffield Children’s Hospital, Sheffield, UK

Nathalie Boddaert Head of department, Pediatric Radiology, Necker-Enfants Malades, Paris, France

Aabir Chakraborty Lead for Paediatric Neurosurgery, Southampton General Hospital, Southampton, UK

Russell Dale Petre Associate Professor Paediatric Neurology Research, Paediatrics & Child Health, Children’s Hospital, University of Sydney, Westmead, Australia

Bernard Dan Professor of Neuroscience, Université libre de Bruxelles (ULB), Brussels; Director of Rehabilitation, Rehabilitation Hospital Inkendaal, Vlezenbeek, Belgium

Linda De Meirleir Head of Pediatric Neurology and Metabolic Diseases and Medical Coordinator for Rare Disorders, Universitair Ziekenhuis Brussel, Brussels, Belgium

Linda S de Vries Professor in Neonatal Neurology, Department of Neonatology, UMCU, Utrecht, the Netherlands

Gabrielle deVeber Professor, Alberta Children’s Hospital Research Institute, University of Calgary, Canada

Michael S. Duchowny Emeritus Director, Comprehensive Epilepsy Program, Nicklaus Children’s Hospital, Miami, Florida, USA

Adré J Du Plessis Chief, Division of Fetal and Transitional Medicine; Director, Fetal Medicine Institute, Children’s National Medical Center, George Washington University School of Medicine, Washington DC, USA

Michael Eyre Specialty Registrar in Paediatric Neurology, Great Ormond Street Hospital, London, UK

Emilio Fernandez-Alvarez Hospital Sant Joan de Deu Servico de Neuropediatria, Barcelona, Spain

Robert Forsyth NHS Consultant Paediatric Neurologist, Great North Children’s Hospital; Senior Lecturer, Newcastle University, Newcastle, UK

Patricia Franco Pediatric Sleep Unit & INSERM U1028, Mother-Children Hospital, University of Lyon 1, France

Paddy Grattan-Smith Clinical Associate Professor, Paediatrics & Child Health, Children’s Hospital, Westmead, Sydney, Australia

Richard Hayward Professor, Paediatric Neurosurgery, Great Ormond Street Hospital for Children, NHS Foundation Trust, London, UK

Cheryl Hemingway Paediatric Neurology Consultant, Great Ormond Street Hospital, London, UK

Michael V Johnston Chief Medical Officer and Blum Moser Endowed Chair for Pediatric Neurology, Kennedy Krieger Institute; Professor of Neurology, Pediatrics and Physical Medicine and Rehabilitation, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

Colin Kennedy Professor in Neurology and Paediatrics, University of Southampton, UK

Adam Kirton Associate Professor, Pediatrics and Clinical Neurosciences Cumming School of Medicine, University of Calgary, Alberta Children’s Hospital Research Institute (ACHRI); Director, Calgary Pediatric Stroke Program Pediatric Neurologist, Alberta Children’s Hospital, Calgary, Alberta, Canada

Ingeborg Krageloh-Mann Professor of Paediatrics; Director Paediatric Neurology and Developmental Medicine, University Children’s Hospital, Tübingen, Germany

Kenneth J Mack Mayo Clinic, Child and Adolescent Neurology, Rochester, Minnesota, USA

AUTHORS’ APPOINTMENTS

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Carey Matsuba University of Bristish Columbia, Vancouver, Canada

Miriam Martinez-Biarge Neonatologist, Imperial College London, London, UK

Manoj Menezes Staff Specialist in Neurology, T.Y. Nelson Department of Neurology and Neurosurgery, The Childrend Hospital at Westmead; Senior Clinical Lecturer, The University of Sydney, Australia

Robert Minns Emeritus Professor of Paediatric Neurology and Hon. Professorial Fellow, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK

Francesco Muntoni Professor, The Dubowitz Neuromuscular Centre, UCL Great Ormond Street, Institute of Child Health, London, UK

Kathryn N North Professor, Murdoch Childrens Research Institute, University of Melbourne, Royal Children’s Hospital, Melbourne, Australia

Anne O’Hare The Salvesen Mindroom Centre, Child Life & Health, University of Edinburgh, Edinburgh, UK

Robert Ouvrier Emeritus Professor, Paediatrics & Child Health, Children’s Hospital, The University of Sydney, Westmead, Australia

Karine Pelc Consultant Paediatric Neurologist, Centre Hospitalier Universitaire Saint Pierre, Université libre de bruxelles (ULB), Brussels, Belgium

Eleni Panagiotakaki Monique M Ryan

Hospices Civils de Lyon, Lyons, France

Director, Department of Neurology, Royal Children’s Hospital, Melbourne, AustraliaVictoria San Antonio Arce Head of the Epilepsy, Sleep and Neurophysiology Section, Neurology Service, Sant Joan de Déu

Barcelona Children’s Hospital, Barcelona, Spain

Christian Sainte-Rose Université Paris Descartes and Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Service de Neurochirurgie Pédiatrique, Paris, France

Mariacristina Scoto Specialty Doctor in Neuromuscular; Honorary Senior Clinical Research Associate, The Dubowitz Neuromuscular Unit, UCL Great Ormond Street Institute of Child Health & GOSH, London, UK

Bruce K. Shapiro Professor of Pediatrics, The Johns Hopkins University School of Medicine; Vice President, Training, Kennedy Krieger Institute, Baltimore, USA

Marc Tardieu Department of Neuropediatrics, Hopital Bicetre, Le Kremlin Bicetre, France

Roberto Tuchman Chief, Department of Neurology, Nicklaus Children’s Hospital, Miami Children’s Health System, Miami, USA

Dominic NP Thompson Consultant Paediatric Neurosurgeon, Department of Neurosurgery, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK

David Walker Neurosurgeon, BrizBrain & Spine Clinic, The Wesley Hospital, Auchenflower, Australia

Andrew Whitelaw Emeritus Professor of Neonatal Medicine, University of Bristol, Bristol, UK

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SAMPLE MATERIAL FROM CHAPTER 6

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Craniosynostosis/ Paediatric Craniovertebral AnomaliesRichard Hayward FRCS

IntroductIonCraniosynostosis is defined here as the premature closure of one or more of the skull vault sutures. While advances in molecular genetics have revolutionised our understanding of the various syndromes that may include craniosynostosis, and improved imaging techniques have provided new information about not only the calvarial sutures but also changes affect-ing the skull base and facial skeletons, the initial diagnosis (or more accurately the initial suspicion) of craniosynostosis still depends primarily on the patient’s – usually a child’s – appearance.

The aim of this chapter is to provide for the paediatric neurologist a broad overview of this complex subject. For convenience craniosynostosis affecting a single vault suture (sometimes referred to as ‘simple’ synostosis) will be dealt with separately from the various complex/syndromic forms in which premature closure of several – sometimes all – of the skull sutures is usual although overlap between the two groups is not uncommon. Johnson and Wilkie have provided a useful overview from a craniofacial surgeon and geneticist’s perspec-tive (Johnson and Wilkie 2011).

AetIology of crAnIosynostosIsThe various causes of craniosynostosis (or conditions with which it may be associated) can be broadly classified as shown in Table 6.1.

single suture synostosisThe direct consequences of premature fusion of a single skull vault suture are for the most part cosmetic – the result of a usually characteristic alteration in head shape. Effects on the facial skeleton, if any, are modest and severe functional conse-quences affecting vision, breathing and feeding, for example, are rare. This is in marked contrast to the complex/syndromic forms of craniosynostosis in which such issues are common.

AetiologyWhile the majority of cases of single suture synostosis arise as isolated events the possible genetic implications of the diagnosis should not be overlooked particularly for unicoronal synostosis (Moloney et al. 1997) (see Unicoronal [and Fron-to-Sphenoidal] Synostosis). Whereas no common candidate genes are presently known for isolated sagittal and metopic synostosis, it is essential that all children with unicoronal syn-ostosis are referred for evaluation by a geneticist (Johnson and Wilkie 2011).

table 6.1

primary Idiopathic No genetic cause either known or suspecteda

Genetic cause known or suspected

Gene mutationb

Chromosomal abnormalityc

Secondary Metabolic: Vitamin D deficient rickets

Hyperthyroidism

Disorders of bone metabolism

Cranio-meta/diaphyseal dysplasia

Osteopetrosis

Storage disorders Hurler syndrome

Morquio syndrome

Drug induced: Metopic synostosis, as part of the fetal valproate syndrome

Physical distortion: Post-CSF shunting positional scaphocephaly

aThe majority of single suture synostosis fall into this category – in particular those affecting the sagittal and metopic sutures.bThis includes not only the syndromes once described eponymously (Crouzon, Apert etc.) but also many previously labelled as non-syndromic that have now had their underlying gene mutation mapped.cThe metopic suture appears to be the most vulnerable when craniosynos-tosis forms part of a chromosomal abnormality – a deletion of part of the short arm of 7, for example.CSF, cerebrospinal fluid

9Chapter 6 Craniosynostosis/Paediatric Craniovertebral Anomalies 5

infection, for example) never absent from what is never a minor cranial operation.

The various surgical interventions (and their timing) currently employed in the management of each single suture synostosis are here briefly described. For a more detailed summary, see the review by Garza and Khosla (2012).

sagittal synostosisPremature closure of the sagittal suture is the most frequent form of craniosynostosis and leads to a characteristic scapho-cephalic (boat-shaped) deformity of the skull. A prevalence of approximately 1 in 5 000 children has been estimated and the condition is more frequently seen in boys. Six per cent of cases are familial with transmission following an autosomal domi-nant pattern with a penetrance of 38% (Lajeunie et al. 1996).

The affected skull has an increased antero-posterior diam-eter, its bi-parietal diameter is reduced (Fig. 6.1) and a bony ridge can often be both seen and felt along the line of the fused suture. Victims of teasing may be called ‘peanut head’. The synostotic process does not always involve the entire suture and even when it does the severity with which the child’s head shape is affected is very variable, with a mild prominence of the forehead at one end of the spectrum to gross elongation (frontal and occipital bossing) plus narrowing (particularly in the pterional regions) at the other.

The variety of surgical treatments presently employed for the correction of sagittal synostosis (for those children whose parents have opted for intervention) suggests either that all are equally effective – or equally non-effective! The operations vary in scale from removal of the fused suture (suturectomy) combined with internal springs (de Jong et al. 2013) or exter-nal (helmet/orthosis) manoeuvres (Proctor 2012) designed to induce a more round shape (all of which need to be performed

before six months of age to be most effective) to increasingly major forms of skull reconstruction for which there are no age limits.

unicoronal (and fronto-sphenoidal) synostosisCraniosynostosis of a single coronal suture produces a charac-teristic asymmetry of the forehead: frontal plagiocephaly. The supra-orbital ridge on the affected side is recessed as is the forehead above while the temporal region is unusually prom-inent. On the contralateral side the frontal region is often bossed, accentuating the asymmetry and the nose is set an angle, its root ‘pointing’ towards the side of the affected suture. The net result is to give the face a characteristic ‘scoliosis’ or curve convex to the affected side. The anterior skull base is also curved – but concave to the affected side (Fig. 6.2).

The elevation of the lateral wing of the sphenoid bone on the affected side is responsible for the characteristic ‘harlequin eye’ appearance on an antero-posterior skull X-ray. The deformation of the orbit results in a subtle malposition of the extra-occular muscle attachments that may in turn cause a complex abnormality of eye movement and a secondary compensatory head tilt (Gosain et al. 1996). All children with unicoronal synostosis should therefore be referred to a paediatric ophthalmologist.

Although the cause of unicoronal synostosis is in many cases unknown it can result from a variety of genetically mediated disorders. Most prominent amongst these is the Muenke (or FGFR3-associated synostosis) (Muenke et al. 1997). Saethre– Chotzen syndrome (Reardon and Winter 1994) and cranio- frontonasal dysplasia (Cohen, Jr 1979) may also involve premature closure of a single coronal suture but their other features are usually sufficiently characteristic to suggest the diagnosis.

Figure 6.1 Three-dimensional CT scans showing the typical scaphocephalic head shape caused by sagittal synostosis.

Figure 6.2 Three-dimensional CT scan showing the typical deformity caused by unicoronal synostosis.

10 Part III Neurological Consequences of Prenatal, Perinatal and Early Postnatal Interference with Brain Development8

developmental and learning difficulties. Marked intellectual compromise was present in 3% of Kreiborg’s series (Kreiborg 1981).

Apert syndromeThe child with Apert syndrome has a head that is tall and shortened from front to back (turri-brachycephaly), midfa-cial (maxillary) retrusion, proptosis, a downward cant to the palpebral fissures and hypertelorism (Lajeunie et al. 1999) (Fig. 6.6a). The essential clinical feature however is a complex fusion (syndactyly) of the fingers and toes (Anderson et al. 1997d, Anderson et al. 1999, Cohen and Kreiborg 1995b) that may require multiple surgical procedures before func-tional effectiveness is achieved (Guero et al. 2004) (Fig. 6.6b). Visceral (Cohen and Kreiborg 1993) and cutaneous (Cohen

and Kreiborg 1995a) abnormalities can also occur. Palatal abnormalities (Kreiborg and Cohen 1992) ranging in severity from frank clefts to a bifid uvula are common and occur with a frequency of up to 75% (Peterson and Pruzansky 1974, Slaney et al. 1996). Cervical vertebral fusions that may be progressive occur in over half of affected children although it is unusual for them to become clinically significant (Thompson et al. 1996).

Developmental and learning difficulties are the norm in Apert syndrome although a combination of developmental assessment tools designed for non-Apert children and low societal expectations may overestimate their severity (Shipster et al. 2002). While a small percentage of children may com-plete secondary education (and usually only with assistance in the classroom), many drop out of mainstream education during their primary school years while a small percentage are too affected for the mainstream education system at any-thing above kindergarten level (Patton et al. 1988, Renier et al. 1996).

Pfeiffer syndromeAlthough described separately for historical reasons, the genetic overlap between Pfeiffer and Crouzon syndromes is such that they are now often considered together as ‘Crouzon–Pfeiffer syndrome’.

The ‘traditional’ Pfeiffer syndrome is an autosomal domi-nant condition characterised by suture fusions that range from bicoronal synostosis alone to pan-synostosis (with or without the cloverleaf skull deformity – see next section) (Winter 1994). Affected patients also have digital abnormalities (Pan-thaki and Armstrong 2003) that include curved and short-ened thumbs and great toes (Anderson et al. 1998b) and, less commonly, digital fusions (although to a lesser degree than in Apert syndrome [Panthaki and Armstrong 2003]).

Cohen (1993) divided children with Pfeiffer syndrome into three types based on their clinical severity. Type 1, those least affected, may display little more than bicoronal synostosis and midface retrusion (in addition to their digital

Figure 6.5 Three-dimensional CT of a child with Crouzon syndrome showing the typical facial appearance. Note also the enlarged scalp veins suggesting raised intracranial pressure secondary to intracra-nial venous hypertension.

Figure 6.6 (a) Apert syndrome. Syndactyly. (b) Three-dimensional CT showing the typical facial features. Figure 6.7 The typical hallux deformity of Pfeiffer syndrome.

(a) (b)

11Part III Neurological Consequences of Prenatal, Perinatal and Early Postnatal Interference with Brain Development14

ed chromosomal abnormalities. It may also occur as a post- operative complication, a consequence of the frontal lobe retraction required during fronto-facial monobloc and bipar-tition procedures in children with severe frontal bone reces-sion (Cobb et al. 2013).

cosmesisThe cosmetic disabilities that most trouble patients with syn-dromic synostosis and their families include a misshapen fore-head, eyes that protrude, eyes set too far apart (hypertelorism) and an upper jaw set back while the lower jaw protrudes.

When correcting for cosmesis alone it is important to remember that surgery carried out on a part of the craniofacial skeleton that is still growing may need to be repeated either wholly or in part in order to achieve a result that will prove stable over time. Our own policy, based more on clinical observation than measurement, is to assume that a forehead and supra-orbital region in a satisfactory configuration at around 10 years of age is unlikely to need further correction and essentially cosmetic reconstructions after that age can focus more on the maxilla and mandible where growth will continue until secondary dentition is complete – the mid to late teens.

conclusIonPrimary craniosynostosis whether it affects one or multiple sutures and is associated or not with a particular syndrome is rare and its management should only be undertaken by a unit with sufficient experience to ensure affected children achieve their developmental potential.

Early assessment by such a unit will enable the correct diagnosis (both genetic and clinical) to be made, the risk of complications assessed and a management plan made that is tailored to each individual child’s needs.

While in non-syndromic unisutural synostosis treatment may require no more than a single reconstructive operation, more complex cases require input from a wide range of spe-cialists including the paediatric neurologist often until the completion of skeletal maturity.

referencesAbou-Sleiman PM, Apessos A, Harper JC, Serhal P, Delhanty JD

(2002) Pregnancy following preimplantation genetic diagnosis for Crouzon syndrome. Mol Hum Reprod 8: 304–9.

Agochukwu NB, Solomon BD, Gropman AL, Muenke M (2012) Epilepsy in Muenke syndrome: FGFR3-related craniosynostosis. Pediatr Neurol 47: 355–61.

Ahmed J, Marucci D, Cochrane L, Heywood RL, Wyatt ME, Leigh-ton SE (2008) The role of the nasopharyngeal airway for obstruc-tive sleep apnoea in syndromic craniosynostosis. J Craniofac Surg 19: 659–63.

Alden TD, Lin KY, Jane JA (1999) Mechanisms of premature closure of cranial sutures. Childs Nerv Syst 15: 670–5.

Allam KA, Wan DC, Khwanngern K, et al. (2011) Treatment of apert syndrome: A long-term follow-up study. Plast Reconstr Surg 127: 1601–11.

Anderson PJ (1997) Crouzon syndrome: Anomalies not limited to the skull and the face. J Craniomaxillofac Surg 25: 356–7.

Anderson PJ, Hall C, Evans RD, Harkness WJ, Hayward RD, Jones BM (1997a) The cervical spine in Crouzon syndrome. Spine 22: 402–5.

Anderson PJ, Hall CM, Evans RD, Hayward RD, Harkness WJ, Jones BM (1997b) The cervical spine in Saethre-Chotzen syn-drome. Cleft Palate Craniofac J 34: 79–82.

Anderson PJ, Hall CM, Evans RD, Hayward RD, Jones BM (1996a) The hands in Saethre-Chotzen syndrome. J Craniofac Genet Dev Biol 16: 228–33.

Anderson PJ, Hall CM, Evans RD, Hayward RD, Jones BM (1998a) The elbow in syndromic craniosynostosis. J Craniofac Surg 9: 201–6.

Anderson PJ, Hall CM, Evans RD, Hayward RD, Jones BM (1999) The feet in Apert’s syndrome. J Pediatr Orthop 19: 504–7.

Anderson PJ, Hall CM, Evans RD, Jones BM, Harkness W, Hayward RD (1996b) Cervical spine in Pfeiffer’s syndrome. J Craniofac Surg 7: 275–9.

Anderson PJ, Hall CM, Evans RD, Jones BM, Hayward RD (1998b) The feet in Pfeiffer’s syndrome. J Craniofac Surg 9: 83–7.

Anderson PJ, Harkness WJ, Taylor W, Jones BM, Hayward RD (1997c) Anomalous venous drainage in a case of non-syndromic craniosynostosis. Childs Nerv Syst 13: 97–100.

Anderson PJ, Smith PJ, Jones BM (1997d) New classification for the hand anomalies in Apert’s syndrome. J Hand Surg Br 22: 140–1.

Antley R, Bixler D (1975) Trapezoidocephaly, midfacial hypoplasia and cartilage abnormalities with multiple synostoses and skeletal fractures. Birth Defects Orig Artic Ser 11: 397–401.

Bellus GA, Gaudenz K, Zackai EH, et al. (1996) Identical muta-tions in three different fibroblast growth factor receptor genes in autosomal dominant craniosynostosis syndromes. Nat Genet 14: 174–6.

Bottero L, Lajeunie E, Arnaud E, Marchac D, Renier D (1998) Functional outcome after surgery for trigonocephaly. Plast Reconstr Surg 102: 952–8.

Bradley JP, Kawamoto HK, Taub P, Wexler A, Cahan L (2003) Antley-Bixler syndrome: Correction of facial deformities and long-term survival. Plast Reconstr Surg 111: 1454–60.

Britto JA, Chan JC, Evans RD, Hayward RD, Jones BM (2001a) Differential expression of fibroblast growth factor receptors in human digital development suggests common pathogenesis in complex acrosyndactyly and craniosynostosis. Plast Reconstr Surg 107: 1331–8.

Britto JA, Evans RD, Hayward RD, Jones BM (1998) Maxillary dis-traction osteogenesis in Pfeiffer’s syndrome: urgent ocular pro-tection by gradual midfacial skeletal advancement. Br J Plast Surg 51: 343–49.

Britto JA, Evans RD, Hayward RD, Jones BM (2001b) From gen-otype to phenotype: the differential expression of FGF, FGFR, and TGFbeta genes characterizes human cranioskeletal develop-ment and reflects clinical presentation in FGFR syndromes. Plast Reconstr Surg 108: 2026–39.

Britto JA, Moore RL, Evans RD, Hayward RD, Jones BM (2001c) Negative autoregulation of fibroblast growth factor receptor 2 expression characterizing cranial development in cases of Apert (P253R mutation) and Pfeiffer (C278F mutation) syndromes and suggesting a basis for differences in their cranial phenotypes. J Neurosurg 95: 660–73.

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Aicardi’s Diseases of the Nervous System in Childhood4th Edition

Edited by Alexis Arzimanoglouwith Anne O’Hare, Michael Johnston and Robert Ouvrier

New edition completely updated and revised. Now in full colour.

Contact us at admin@mackeith.co.uk to receive further details. June 2017 / Hardback / 928 pp / 280 x 205mm, 4-colour / ISBN 978-1-909962-80-4 / £199.95www

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